The present invention relates to a biologically compatible collagenous reaction product comprising ethylenically unsaturated or polymers substituted collagen. More particularly, the invention relates to a collagenous reaction product that can be polymerized to form shaped articles useful in medical applications, including implants for ophthalmology, surgery, orthopedics and cardiology.
Various methods and materials have been proposed for modifying collagen to render it more suitable for biological and medical procedures. (See, e.g., Lloyd et al., "Covalent Bonding of Collagen and Acrylic Polymers," American Chemical Society Symposium on Biomedical and Dental Applications of Polymers, Polymer Science and Technology, Vol. 14, Plenum Press (Gebelein and Koblitz, eds.), New York, 1980, pp. 59-84; Shimizu et al., Biomat. Med. Dev. Art. Org., 5(1):49-66 (1977); and Shimizu et al., Biomat. Med. Dev. Art. Org., 6(4):375-391 (1978), for general discussion on collagen and synthetic polymers.)
In U.S. Pat. Nos. 4,427,808 and 4,563,490, Stol et al. disclose composite polymeric materials and methods for preparing such materials. The polymeric materials consist of a hydrophilic polymer or copolymer based on methacrylic or acrylic esters, fibrillar collagen and a crosslinking agent. The polymeric materials are not reacted with the fibrillar collagen. Rather, the collagen is dispersed unreacted in the hydrophilic polymer, the latter forming a matrix that is penetrated by the collagen.
In U.S. Pat. No. 3,453,222, Young discloses methods of chemically modifying proteinaceous materials, e.g., collagen, by reaction under mild alkaline conditions with alkane and alkene sultones, e.g., 3-hydroxy-1-propene sulfonic acid sultone. Young's disclosed sultone modified protein products and methods are not useful in biological and medical procedures due to their low biocompatibility.
In U.S. Pat. Nos. 4,388,428 and 4,452,925, Kuzma et al. disclose polymerized hydrophilic water-swellable compositions made from a mixture of components consisting essentially of inter alia solubilized collagen and ethylenically unsaturated monomers containing nitrogen. (See also PCT Int. Appl. No. PCT/US82/00889, published Feb. 3, 1983 as WO 83/00339). A severe drawback to Kuzma et al.'s compositions which limits their usefulness as biological materials is the presence of significant quantities of acrylamides, known neurotoxins, as ethylenically unsaturated monomers. No recognition of the neurotoxicity of acrylamides is made in any of these patent.
Miyata et al., U.S. Pat. No. 4,215,200, describes chemically modified polymeric collagen hemostatic agents in powder and gel forms. The specific polymeric collagen is said to assume regularly staggered quaternary structure and a high positive electrostatic charge at physiological pH, i.e., about 7.4, when guanidinated, esterified, and/or esterified-guanidinated. No mention or suggestion is made in the '200 patent as to acylating collagen to obtain collagenous materials with plastic-like properties.
In other developments, U.S. Pat. No. 4,264,155 (issued to Miyata) discloses soft contact lenses made from collagen gels to which water-soluble organic polyhydroxy polymers, e.g., mucopolysaccharides, polyvinyl alcohols and the like are added, followed by chemical crosslinking of the gels. The polyhydroxy polymeric additives are said to "surround" the strands of the collagen molecules to protect them against microbial degradation. No teaching or suggestion is made in U.S. Pat. No. 4,264,155 of possibly acylating collagen to produce ethylenically unsaturated or polymers substituted collagen which could then be polymerized to form useful biomedical articles having high biological and tissue acceptability.